PDF(Pubmed)
Abstract：
Obesity is a negative prognosis factor for breast cancer. Yet, the biological mechanisms underlying this effect are still largely unknown. An emerging hypothesis is that the transfer of free fatty acids (FFA) between adipocytes and tumor cells might be altered under obese conditions, contributing to tumor progression. Currently there is a paucity of models to study human mammary adipocytes (M-Ads)-cancer crosstalk. As for other types of isolated white adipocytes, herein, we showed that human M-Ads die within 2-3 days by necrosis when grown in 2D. As an alternative, M-Ads were grown in a fibrin matrix, a 3D model that preserve their distribution, integrity and metabolic function for up to 5 days at physiological glucose concentrations (5 mM). Higher glucose concentrations frequently used in in vitro models promote lipogenesis during M-Ads culture, impairing their lipolytic function. Using transwell inserts, the matrix embedded adipocytes were cocultured with breast cancer cells. FFA transfer between M-Ads and cancer cells was observed, and this event was amplified by obesity. Together these data show that our 3D model is a new tool for studying the effect of M-Ads on tumor cells and beyond with all the components of the tumor microenvironment including the immune cells.
摘要：
肥胖是乳腺癌的不良预后因素。然而，这种效应的生物学机制在很大程度上仍然未知.一个新兴的假设是，在肥胖条件下，脂肪细胞和肿瘤细胞之间的游离脂肪酸（FFA）的转移可能会发生变化。有助于肿瘤进展。目前，研究人类乳腺脂肪细胞（M-Ads）-癌症串扰的模型很少。至于其他类型的分离的白色脂肪细胞，在这里，我们表明，人M-Ads在2-3天内死亡坏死时，在2D中生长。作为替代,M-Ads在纤维蛋白基质中生长，保留其分布的3D模型，在生理葡萄糖浓度（5mM）下长达5天的完整性和代谢功能。在体外模型中经常使用的较高的葡萄糖浓度促进M-Ads培养过程中的脂肪生成，损害他们的脂肪分解功能。使用transwell插入物，基质包埋的脂肪细胞与乳腺癌细胞共培养。观察到M-Ads和癌细胞之间的FFA转移，肥胖加剧了这一事件。这些数据表明，我们的3D模型是一种新的工具，用于研究M-Ads对肿瘤细胞的影响，以及包括免疫细胞在内的肿瘤微环境的所有成分。
